SEATTLE--(BUSINESS WIRE)--Alpine Immune Sciences, Inc. (Alpine), a biotechnology company
developing a next-generation immune modulation platform, today announced
results from a preclinical study evaluating first-generation variant Ig
domains (vIgDs™) from the company’s lead program, ALPN-101. These vIgDs
consisted of an ICOS ligand-based inhibitory domain engineered to
acquire CD28 modulatory properties, creating a potential first-in-class
dual ICOS/CD28 pathway inhibitor. Results presented demonstrate
meaningful activity in an aggressive animal model of graft vs. host
disease (GvHD), suggesting that the ALPN-101 program and other Alpine
vIgDs could potentially have clinical therapeutic utility in multiple
inflammatory diseases. The data will be presented today in a poster
session at FOCiS 2017, the annual meeting of the Federation of Clinical
Immunology Societies, in Chicago.

“This study demonstrates meaningful activity in an animal model of one
of Alpine’s first-generation vIgDs, part of the ALPN-101 development
program. This is noteworthy because there are currently no FDA-approved
therapies for the treatment of GvHD, and the severity of the disease
model suggests that ALPN-101 vIgDs may be useful for other inflammatory
conditions as well,” said Stanford Peng, M.D., Ph.D., executive vice
president of Research and Development and chief medical officer of
Alpine.

Additional preclinical studies are currently underway with Alpine’s
second- and third-generation ALPN-101 vIgDs, with results expected to be
presented in an upcoming scientific forum.

GvHD currently has no FDA-approved treatment options, and has a major
impact on survival following transplantation. Transplant-related
mortality is as high as 92 percent in grade IV acute GvHD. Approximately
30 to 50 percent (2,500 - 4,200 per year in the U.S.) of bone marrow
transplant patients will develop clinically significant GvHD.

“These preclinical data suggest directed evolution of immuno-modulatory
domains via our vIgD platform can provide the basis for novel
therapeutics for the treatment of GvHD and other serious inflammatory
conditions,” said Mitchell H. Gold, M.D., executive chairman and chief
executive officer of Alpine. "With our upcoming merger with Nivalis
Therapeutics, we expect to have significant resources to accelerate the
development of our platform into other promising areas for both
inflammation and oncology applications.”

Preclinical Study Design and Results

The immunoglobulin superfamily (IgSF) is a large, diverse family of
proteins expressed on immune cells that play a critical role in
regulating the immune system. These proteins have been extensively
studied in cancers and autoimmune diseases. Most therapeutic strategies
targeting this family of proteins have employed monoclonal antibodies
binding to a single receptor on a cell. In contrast, Alpine’s vIgD
platform seeks to engineer human IgSF extracellular domains, potentially
tailoring their affinity to multiple but specific target ligands.

In the preclinical study presented at FOCiS 2017, Fc fusion proteins
incorporating these evolved immunomodulatory IgSF domains were tested in
vitro and in vivo. Belatacept, an FDA-approved
immunosuppressive T-cell co-stimulation blocker, was used for comparison.

Results showed that in an animal model Alpine’s novel first-generation
ICOS/CD28 dual antagonist vIgDs were more potent than belatacept in
attenuating T cell activation in vitro as assessed by proliferation and
cytokine production. Alpine’s first-generation ICOS/CD28 vIgD molecule
also significantly reduced markers of disease activity in an animal
model of GvHD as assessed by a standard disease activity score
(comprised of overall health and activity, skin and hair changes, and
body weight loss).

Alpine’s Planned Merger with Nivalis Therapeutics

In April 2017, Alpine and Nivalis Therapeutics, Inc. (NASDAQ:NVLS)
announced that they had entered into a definitive merger agreement under
which Alpine will merge with and into a wholly-owned subsidiary of
Nivalis in an all-stock transaction with the surviving company named
‘Alpine Immune Sciences, Inc.’ and trading on the NASDAQ under the
ticker symbol ‘ALPN’. The merger will result in a combined company with
a novel protein-based discovery platform focused on inflammation and
immuno-oncology. The merger is expected to close in the third quarter of
2017, subject to the approval of the stockholders of each company and
the satisfaction or waiver of other customary conditions.

About Alpine Immune Sciences, Inc.

Alpine Immune Sciences, Inc. was founded in 2015 and is focused on
developing novel protein‐based immunotherapies using its proprietary
variant immunoglobulin domain (vIgD) platform technology. The vIgD
platform is designed to create novel therapeutics that modulate multiple
therapeutic targets, including many present in the immune synapse.
Alpine's vIgDs are developed using a unique process known as directed
evolution, which can produce proteins capable of either enhancing or
diminishing an immune response and thereby may apply therapeutically to
both oncology and inflammatory diseases. Alpine has also developed its
transmembrane immunomodulatory protein (TIP™) technology, based on the
vIgD platform, to enhance engineered cellular therapies. In October
2015, Alpine signed a worldwide research and license agreement with Kite
Pharma, Inc. (NASDAQ: KITE) for up to $535 million in upfront and
potential milestone payments and, in addition, royalties on resulting
sales. The agreement allows Kite access to certain targets developed
using Alpine's TIP platform. For more information visit www.alpineimmunesciences.com/.

About Nivalis Therapeutics, Inc.

Nivalis Therapeutics, Inc. (http://www.nivalis.com)
is a pharmaceutical company that has historically been focused on the
discovery and development of product candidates for patients with cystic
fibrosis, or CF. Nivalis’ development candidates selectively target an
enzyme known as S-nitrosoglutathione reductase (GSNOR). GSNOR regulates
levels of an endogenous protein known as S-nitrosoglutathione, or GSNO.
Depleted levels of GSNO have been associated with CF, asthma,
inflammatory bowel diseases and certain cardiovascular diseases.
Following recent disappointing results of a Phase 2 clinical trial of
its lead product candidate, cavosonstat, in CF, Nivalis determined to
not pursue the development of this compound in CF and to wind down its
research and development activities while devoting its efforts to
investigating and evaluating strategic alternatives.

Forward-Looking Statements

This communication contains forward-looking statements (including
within the meaning of Section 21E of the United States Securities
Exchange Act of 1934, as amended, and Section 27A of the United States
Securities Act of 1933, as amended) concerning Nivalis, Alpine
(including Alpine’s platform technology, potential therapies, clinical
and regulatory objectives and milestone and royalty payment potential),
the proposed merger transaction between Nivalis and Alpine and other
matters. These statements may discuss goals, intentions and expectations
as to future plans, trends, events, results of operations or financial
condition, or otherwise, based on current beliefs of the managements of
Nivalis and Alpine, as well as assumptions made by, and information
currently available to, management of Nivalis and Alpine.
Forward-looking statements generally include statements that are
predictive in nature and depend upon or refer to future events or
conditions, and include words such as “may,” “will,” “should,” “would,”
“expect,” “plan,” “believe,” “intend,” “look forward,” and other similar
expressions among others. Statements that are not historical facts are
forward-looking statements. Forward-looking statements are based on
current beliefs and assumptions that are subject to risks and
uncertainties and are not guarantees of future performance. Actual
results could differ materially from those contained in any
forward-looking statement as a result of various factors, including,
without limitation, that the conditions to the closing of the merger
transaction are not satisfied, that available cash is lower than
estimated, that Alpine’s discovery-stage and preclinical program do not
advance into the clinic or result in approved products on a timely or
cost effective basis or at all. The foregoing review of important
factors that could cause actual events to differ from expectations
should not be construed as exhaustive and should be read in conjunction
with statements that are included herein and elsewhere, including the
risk factors included inNivalis’registration statement
on Form S-4, including the proxy statement/prospectus/information
statement therein, Nivalis’ most recent Annual Report on Form 10-K, and
Nivalis’ recent Quarterly Report on Form 10-Q and Current Reports on
Form 8-K filed with the Securities and Exchange Commission (the “SEC”).
Neither Nivalis nor Alpine can give any assurance that the conditions to
the merger transaction will be satisfied. Except as required by
applicable law, neither Nivalis nor Alpine undertakes any obligation to
revise or update any forward-looking statement, or to make any other
forward-looking statements, whether as a result of new information,
future events or otherwise.

No Offer or Solicitation

This communication is not intended to and does not constitute an offer
to sell or the solicitation of an offer to subscribe for or buy or an
invitation to purchase or subscribe for any securities or the
solicitation of any vote in any jurisdiction pursuant to the proposed
transaction or otherwise, nor shall there be any sale, issuance or
transfer of securities in any jurisdiction in contravention of
applicable law. No offer of securities shall be made except by means of
a prospectus meeting the requirements of Section 10 of the United States
Securities Act of 1933, as amended. Subject to certain exceptions to be
approved by the relevant regulators or certain facts to be ascertained,
the public offer will not be made directly or indirectly, in or into any
jurisdiction where to do so would constitute a violation of the laws of
such jurisdiction, or by use of the mails or by any means or
instrumentality (including without limitation, facsimile transmission,
telephone and the internet) of interstate or foreign commerce, or any
facility of a national securities exchange, of any such jurisdiction.

Additional Information about the Merger and Where to Find It

In connection with the proposed merger, Nivalis has filed a registration
statement on Form S-4 with the SEC, including a proxy
statement/prospectus/information statement.. The proxy
statement/prospectus/information statement and any other relevant
documents filed by Nivalis with the SEC may be obtained free of charge
through the website maintained by the SEC at www.sec.gov.
In addition, investors and stockholders may obtain free copies of the
documents filed by Nivalis with the SEC (when they become available) by
directing a written request to: Nivalis Therapeutics, Inc., PO Box
18387, Boulder, Colorado 80308, Attention: Investor Relations. Investors
and stockholders are urged to read the proxy
statement/prospectus/information statement and the other relevant
materials before making any voting or investment decision with respect
to the proposed merger.

Participants in the Solicitation

Nivalis and Alpine, and each of their respective directors and executive
officers and certain of their other members of management and employees,
may be deemed to be participants in the solicitation of proxies in
connection with the proposed transaction. Information about Nivalis’
directors and executive officers is included in Nivalis’ Annual Report
on Form 10-K for the year ended December 31, 2016, filed with the SEC on
February 13, 2017, and the proxy statement for Nivalis’ 2017 annual
meeting of stockholders, filed with the SEC on April 6, 2017. Additional
information regarding these persons and their interests in the
transaction is included in the proxy statement/prospectus/information
statement referred to above.